FIGHT: A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer

• Sponsor: Five Prime Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03694522
• Collaborator: Zai Lab (Shanghai) Co., Ltd. (Industry)
• Enrollment: 155
• Locations: 189
• Arms: 2
• Actual Duration (Months): 43.9
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The main objective of the Phase 2 part of the study is to evaluate the efficacy of bemarituzumab (FPA144), a targeted antibody, in combination with modified FOLFOX6 compared to placebo in combination with modified FOLFOX6 in participants with advanced gastrointestinal cancer.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Biological: Bemarituzumab; Drug: Placebo; Drug: Modified FOLFOX6	Phase 2

Detailed Description

Study FPA144-004 is a phase 1/2, multicenter, global, double-blind, randomized, controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of bemarituzumab in combination with mFOLFOX6, compared with placebo in combination with mFOLFOX6, in adults with unresectable, locally advanced, or metastatic gastric cancer including cancer of the gastroesophageal junction (GEJ).

This study includes a Phase 1 safety run-in portion and a Phase 2 portion. The Phase 1 safety run-in is an open-label dose-escalation of bemarituzumab + mFOLFOX6 in patients with GI tumors (not FGFR2 selected) that is reported separately (NCT03343301).

The Phase 2 portion of the study (to follow the Phase 1 safety run-in) is described in this record.

Study Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double blinded (participant, treating physician)
• Primary Purpose: Treatment
• Official Title: FIGHT: A Phase 2 Randomized, Double-Blind, Controlled Study Evaluating Bemarituzumab (FPA144) and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Preceded by Dose-Finding in Phase 1
• Actual Study Start Date: Sep 14, 2018
• Actual Primary Completion Date: Sep 23, 2020
• Actual Study Completion Date: May 13, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bemarituzumab + mFOLFOX6 Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Biological: Bemarituzumab; Administered by intravenous infusion over approximately 30 minutes; Other Names: FPA144 ; Drug: Modified FOLFOX6; mFOLFOX6 regimen consists of the following: Oxaliplatin 85 mg/m² IV infusion over 120 minutes Leucovorin 400 mg/m² IV infusion over 120 minutes, or 200 mg/m² levo-leucovorin if leucovorin is unavailable 5-fluorouracil (5-FU) 400 mg/m² bolus over approximately 5 minutes then 5-FU 2400 mg/m² as a continuous IV infusion over approximately 48 hours; Other Names: mFOLFOX6
Placebo Comparator: Placebo + mFOLFOX6 Participants received placebo for bemarituzumab administered every 2 weeks with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Drug: Placebo; Administered by intravenous infusion over approximately 30 minutes; Drug: Modified FOLFOX6; mFOLFOX6 regimen consists of the following: Oxaliplatin 85 mg/m² IV infusion over 120 minutes Leucovorin 400 mg/m² IV infusion over 120 minutes, or 200 mg/m² levo-leucovorin if leucovorin is unavailable 5-fluorouracil (5-FU) 400 mg/m² bolus over approximately 5 minutes then 5-FU 2400 mg/m² as a continuous IV infusion over approximately 48 hours; Other Names: mFOLFOX6

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.]

   PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had ≥ 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization. The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.

Secondary Outcome Measures

1. Overall Survival (OS) [From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.]

   OS is defined as time from randomization until death from any cause. Participants who were lost to follow-up or did not have a date of death were censored at the last date that they were known to be alive. Participants with confirmed death or alive status after the data cutoff date were censored at the data cutoff date.

2. Overall Response Rate (ORR) [Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.]

   Tumor response assessment was performed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. ORR is defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions.

3. Number of Participants With Treatment-emergent Adverse Events [From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 75.0) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 75.6) weeks in the placebo + mFOLFOX6 group.]

   Treatment emergent adverse events are defined as adverse events (AEs) that started or worsened between the start of study drug and 28 days after permanent discontinuation of study drug. A serious AE is defined as any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability or incapacity; Was a congenital anomaly or birth defect. The investigator assessed the causality/relationship between the study treatment and each AE, and assessed the severity of each AE according to the guidelines provided in National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Histologically documented gastric or gastroesophageal junctional adenocarcinoma (not amenable to curative therapy)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

• Adequate hematological, liver and kidney function. Measurable or non-measurable, but evaluable disease using RECIST v1.1

• Fibroblast growth factor receptor 2b (FGFR2b) overexpression as determined by a centrally performed immunohistochemistry tissue test and/or FGFR2 gene amplification as determined by a centrally performed circulating tumor deoxyribonucleic acid (ctDNA) blood based assay

• Candidate for mFOLFOX6 chemotherapy

Key Exclusion Criteria:

• Untreated or symptomatic central nervous system (CNS) metastases

• Clinically significant cardiac disease,

• Peripheral sensory neuropathy >/= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2

• Active infection requiring systemic treatment

• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection

• Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway

• Known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer

• Known positivity for human epidermal growth factor receptor 2 (HER2)

• Women who are pregnant or breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	The Oncology Institute of Tuscon	Tucson	Arizona	United States	85745
3	Marin Cancer Care, Inc-California Cancer Care A Medical Group, Inc	Greenbrae	California	United States	94904
4	Sutter Medical Group	Sacramento	California	United States	95816
5	UCLA Medical Centre - Santa Monica Hematology and Oncology	Santa Monica	California	United States	90404
6	Innovative Clinical Research Institute (ICRI)	Whittier	California	United States	90603
7	Yale Cancer Center	New Haven	Connecticut	United States	06519
8	Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut	Plainville	Connecticut	United States	06062
9	University of Chicago	Chicago	Illinois	United States	60637
10	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
11	University of Kansas Medical Center	Westwood	Kansas	United States	66205
12	Oschsner Clinic Foundation	New Orleans	Louisiana	United States	70121
13	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
14	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
15	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
16	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
17	Josephine Ford Cancer Center-Henry Ford Cancer Center	Detroit	Michigan	United States	48202
18	Summit Medical Group. Morristown Oncology	Morristown	New Jersey	United States	07960
19	University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)	Rochester	New York	United States	14642
20	Stony Brook Cancer Center	Stony Brook	New York	United States	11794
21	Westchester Institute For Treatment Of Cancer & Blood Disorders	White Plains	New York	United States	10601
22	UNC- Chapel Hill	Chapel Hill	North Carolina	United States	27599
23	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina	United States	28374
24	St. Luke's Physician Group - St. Luke's Cancer Care Associates	Bethlehem	Pennsylvania	United States	18015
25	Medical University of South Carolina	Charleston	South Carolina	United States	29435
26	Tennessee Cancer Specialists	Knoxville	Tennessee	United States	37909
27	Arlington Cancer Center	Arlington	Texas	United States	76012
28	Utah Cancer Specialists (Intermountain Hematology - Oncology Associates) UCS Cancer Center	S. Salt Lake	Utah	United States	84106
29	Virginia Mason Seattle Main Clinic	Seattle	Washington	United States	98101
30	Chris O'brien Lifehouse	Camperdown		Australia
31	The Townsville Hospital	Douglas		Australia
32	Sydney Adventist Hospital	Wahroonga		Australia
33	AZ Sint Jan	Brugge		Belgium
34	CH de l'Ardenne	Libramont		Belgium	6800
35	CHC Clinique Saint-Joseph	Liege		Belgium	04000
36	CHU UCL Namur, site Godinne	Yvoir		Belgium	05530
37	Anhui Provincial Cancer Hospital	Hefei	Anhui	China	230031
38	Shiyan Taihe Hospital	Shiyan	Hubei	China	442000
39	Wuhan Union Hospital of China	Wuhan	Hubei	China	430000
40	The 81st Hospital of Chinese PLA	Nanjing	Jiangsu	China	210002
41	Beijing Cancer Hospital	Beijing		China	100412
42	Chinese PLA General Hospital	Beijing		China
43	The First Hospital of Jilin University	Changchun		China	130021
44	Sino Japanese Friendship Hospital of Jilin University	Changchun		China	130033
45	Hunan Cancer Hospital	Changsha		China	410006
46	Xiangya Hospital of Central South University	Changsha		China
47	Chongqing Daping Hospital	Chongqing		China	400000
48	Fujian Cancer Hospital	Fuzhou		China	350014
49	The First Affiliated Hospital, Zhejiang University	Hangzhou		China	310003
50	Sir Run Run Shaw Hospital	Hangzhou		China
51	Zhejiang Cancer Hospital	Hangzhou		China
52	Harbin Medical University Cancer Hopsital	Harbin		China
53	Nanton Tumor Hospital	Nantong		China
54	Shanghai East Hospital	Shanghai		China	200123
55	Fudan University Shanghai Cancer Center	Shanghai		China	210032
56	Ruijin Hospital Affiliated to Shanghai Jiatong University School of Medicine	Shanghai		China
57	Cancer Hospital of Shantou University Medical College	Shantou		China	515041
58	Liaoning Cancer Hospital	Shenyang		China	110042
59	Fourth Hospital of Hebei Medical University	Shijiazhuang		China
60	The Second Affiliated Hospital of Soochow University	Suzhou		China	215004
61	Tianjin Medical University Cancer Institute and Hospital	Tianjin		China	300060
62	Henan Cancer Hospital	Zhengzhou		China	450008
63	CHRU Jean MINJOZ	Besançon		France	25000
64	Chu Morvan - Institut de Cancerologie	Brest		France
65	Hopital Nord France Comte - Site Le Mittan	Montbéliard		France	25200
66	Polyclinique de Gentilly	Nancy		France
67	CHU de Saint Etienne	Saint-Étienne		France	42055
68	Centre de Radiotherapie - Clinique Sainte Anne	Strasbourg		France	67000
69	Centre Paul Strauss	Strasbourg		France
70	Klinik fur Innere Medizin, Shwerpunkt Gastroenterologie, Hamatologie, Onkologie, Nephrologie	Berlin		Germany	12559
71	Stadtisches Klinikum Braunschweig	Braunschweig		Germany	38114
72	Krankenhaus Nordwest gGmbH, Institut fur Klinisch-Onkologische Forschung	Frankfurt am Main		Germany	60488
73	Klinikum Ludwigsburg	Ludwigsburg		Germany	71640
74	Universitatsmedizin Manheim, II. Medizinische Klinik	Mannheim		Germany
75	Klinikum Ostalb, Stauferklinikum Schwabisch Gmund, Zentrum fur Innere Medizin	Mutlangen		Germany
76	Kliniken Nordoberpfalz AG, Klinikum Weiden, Medizinische Klinik I	Oberpfalz		Germany	92637
77	National Institute of Oncology	Budapest		Hungary	1122
78	Del-Pesti Centrumkorhaz - Orszangos Hematologiai es Infektologiai Intezet, Onkologiai Osztaly	Budapest		Hungary
79	Sugarterapias es Klinikai Onkologaiai Intezet B-A-Z Megyei Korhaz	Miskolc		Hungary
80	Josa Andras Teaching Hospital	Nyíregyháza		Hungary	4400
81	University of Pecs, Clinic of Oncotherapy	Pecs		Hungary	7624
82	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet	Szolnok		Hungary	5000
83	AOU Ospedall Riuniti Umberto	Ancona		Italy	60020
84	AO "S.G. Moscati"	Avellino		Italy
85	Centro di Riferimento Oncologico	Aviano		Italy	33081
86	Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia	Brescia		Italy
87	Istituto di Ricovero e Cura a Carattere Scientifico - IRCCS di Candiolo	Candiolo		Italy	10060
88	Azienda Socio-Sanitaria Territoriale di Cremona	Cremona		Italy	26100
89	Azienda Ospedaliero Universitaria Caregg - I S.O.D. Oncologia Medica	Firenze		Italy
90	Ospedale Policlinico S. Martino	Genova		Italy	16132
91	Ospedale Generale Mater Salutis" - Azienda ULSS n. 21 di Legnago	Legnago		Italy	37045
92	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola		Italy	47014
93	Istituto Europeo di Oncologia	Milan		Italy	20141
94	Servizio Oncologia Medica ed Ematologia, AOU dell'Universita	Napoli		Italy	80131
95	Fondazione Irccs Policlinico San Matteo	Pavia		Italy
96	Azienda Ospedaliera Universitaria Pisana	Pisa		Italy
97	Policlinico Universitario Campus Bio-Medico di Roma	Roma		Italy
98	Fondazione IRCSS Casa Sollievo Della Sofferenza	San Giovanni Rotondo		Italy
99	ASST della Valtellina e dell'Alto Lario - PO di Sondrio	Sondrio		Italy
100	A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette	Torino		Italy
101	Azienda Sanitaria Universitaria Integrata de Udine	Udine		Italy	33100
102	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
103	Kagawa University Hospital	Kita-gun	Kagawa	Japan	761-0793
104	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyō-Ku		Japan
105	Hiroshima Citizens Hospital	Hiroshima		Japan	730-8518
106	St. Marianna University School of Medicine Hospital	Kawasaki		Japan	216-8511
107	Japan Community Health Care Organization Kyushu Hospital	Kitakyushu		Japan
108	The Cancer Institute Hospital of JFCR	Koto-Ku		Japan
109	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
110	Hyogo College of Medicine College Hospital	Nishinomiya		Japan	663-8501
111	Osaka General Medical Center	Osaka		Japan	558-8558
112	Osaka Medical College Hospital	Osaka		Japan	569-8686
113	Gangnam Severance Hospital, Yonsei University Health System	Seoul	Gangnam	Korea, Republic of	06273
114	Hallym University Sacred Heart Hospital	Anyang	Gyeonggi-do	Korea, Republic of	14068
115	Seoul National University Bundang Hospital	Seongnam	Gyeonggi	Korea, Republic of	13620
116	Ajou University Hospital	Suwon	Gyeonggi	Korea, Republic of	16499
117	Chonbuk National University Hospital	Jeonju	Jeollabuk-do	Korea, Republic of	54907
118	Gachon University Gil Medical Center	Incheon	Namdong-gu	Korea, Republic of	21565
119	Kyungpook National University Chilgok Hospital	Daegu	North Gyeongsang	Korea, Republic of
120	Dong-A University Hospital	Busan		Korea, Republic of	49201
121	Chungnam National University Hospital (CNUH)	Daejeon		Korea, Republic of	35015
122	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
123	Yonsei University Health System	Seoul		Korea, Republic of	03722
124	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	04514
125	Asan Medical Center	Seoul		Korea, Republic of	05505
126	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
127	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
128	Seoul National University Hospital	Seoul		Korea, Republic of	3080
129	Beskidzkie Centrum Onkologii - Szpital Miejski im. Jana Pawla II w Bielsku-Bialej	Bielsko-Biala		Poland	43-300
130	Szpital Specjalistyczny w Brzozowie, Podkarpacki Osrodek Onkologiczny	Brzozów		Poland	36-200
131	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie	Lublin		Poland
132	SP ZOZ Ministerstwa Spraw Wewnetrznych z Warminsko - Mazurskim Centrum Onkologii	Olsztyn		Poland	10-228
133	Europejskie Centrum Zdrowia Otwock Szpital im. F. Chopina	Otwock		Poland	05-400
134	Lekarz Beata Madej Mruk I Partner. Spolka Partnerska Oddzial nr 1 w Rzesowie	Rzeszów		Poland	35-021
135	Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny Ministerstwa Obronty Narodowej	Warszawa		Poland	04-141
136	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Klinika Onkologi I Radioterapii	Warszawa		Poland
137	Centro Hospitalar do Baixo Vouga, EPE	Aveiro		Portugal	3814-501
138	Hospital de Braga	Braga		Portugal	4710-243
139	Hospital Senhora Da Oliveira EPE	Guimarães		Portugal
140	Centro Hospitalar Universitario do Porto E.P.E	Porto		Portugal	4099-011
141	Instituto Portugues de Oncologia do Porto Francisco Gentil E.P.E	Porto		Portugal
142	Centro Hospitalar de Entre o Douro e Vouga EPE	Santa Maria Da Feira		Portugal
143	Unidade Local de Saude de Matosinhos EPE	Senhora Da Hora		Portugal
144	Institutul Clinic Fundeni - Clinica Pediatrie	Bucharest		Romania	022328
145	S.C. Medisprof S.R.L	Cluj Napoca		Romania	400641
146	Institutul Oncologic, Prof. Dr. I. Chiricuta Cluj-Napoca	Cluj-Napoca		Romania	400015
147	Spitalul Clinic Judetean de Urgenta ,,Sf. Apostol Andrei" Constanta, Clinica Oncologie Medicala	Constanţa		Romania	900591
148	S.C. Centrul de Oncologie Sf. Nectarie S.R.L., Oncologie Medicala	Craiova		Romania	200347
149	SC Oncolab SRL, Oncologie	Craiova		Romania	200385
150	S.C. Oncocenter Oncologie Clinica S.R.L	Timisoara		Romania	300166
151	Complejo Hospitalario Universitario A Coruna	A Coruña		Spain
152	Hospital Universitario Fundacion Alcorcon	Alcorcon		Spain
153	Hospital del Mar	Barcelona		Spain	08003
154	Hospital Duran I Reynals - Instituto Catalan de Oncologia	Barcelona		Spain	08908
155	Hospital de la Santa Creu I Sant Pau	Barcelona		Spain
156	Hospital General de Catalunya	Barcelona		Spain
157	Institut Catala d'Oncologia - Hospital Doctor Josep Trueta	Girona		Spain	17007
158	Hospital Universitari Arnau de Vilanova	Lleida		Spain
159	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
160	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
161	Hospital General Universitario Gregorio Maranon	Madrid		Spain
162	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda		Spain
163	Clinica Universidad de Navarra	Pamplona		Spain	31008
164	Complejo Hospital De Navarra	Pamplona		Spain	31008
165	Corporacio Sanitaria Parc Tauli	Sabadell		Spain
166	Hosptial Universitario Virgen Macarena	Servilla		Spain	41009
167	Hospital Universitario Mutua de Terrassa	Terrassa		Spain	08221
168	China Medical University Hospital	Taichung		Taiwan	40447
169	Faculty of Medicine, Chulalongkorn University	Bankok		Thailand
170	Chiangrai Prachanukroh Hospital	Chiang Rai		Thailand
171	Faculty of Medicine, Prince of Sonkla University	Hat Yai		Thailand	90110
172	Khon Kaen Hospital	Khon Kaen		Thailand
173	Lampang Cancer Hospital	Lampang		Thailand
174	Cukurova University Faculty of Medicine Paediatric Nephrology	Adana		Turkey
175	Hacettepe Universitesi Tip Fakultesi	Ankara		Turkey	06100
176	Ankara Oncology Education and Research Hospital	Ankara		Turkey	06200
177	Ondokuz Mayis University Medicine Faculty	Atakum		Turkey	55200
178	Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi	Aydin		Turkey	09100
179	Uludag Universitesi Tip Fakultesi	Bursa		Turkey	16059
180	Gaziantep Universitesi Tip Fakultesi, Sahinbey Onkoloji Hastanesi	Gaziantep		Turkey
181	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Istanbul		Turkey	34093
182	Istanbul Madeniyet Universitesi Tip Fakultesi	Istanbul		Turkey
183	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey
184	Medical Park Izmir Hastanesi	Izmir		Turkey	35575
185	Ege University Hopsital	Izmir		Turkey
186	Kocaeli Universitesi Tip Fakultesi	Kocaeli		Turkey	41380
187	Inonu Universitesi Tip Fakultesi Turgut Ozal Tip Merkezi	Malatya		Turkey	44300
188	Yuzuncuyil Universitesi Tip Fakultesi	Van		Turkey	65080
189	Ninewells Hospital and Medical School	Dundee		United Kingdom	DD198Y

Sponsors and Collaborators

• Five Prime Therapeutics, Inc.
• Zai Lab (Shanghai) Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 10, 2021
• Statistical Analysis Plan - Oct 20, 2020

More Information

Publications

None provided.

• Responsible Party: Five Prime Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT03694522
• Other Study ID Numbers: FPA144-004 Phase 2
• First Posted: Oct 3, 2018
• Last Update Posted: Jul 6, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Stomach Neoplasms; Bemarituzumab

Study Results

Participant Flow

Recruitment Details	Study FPA144-004 was a Phase 1/2 study. Phase 1 was a safety run-in to determine the recommended dose of bemarituzumab to be administered in combination with a fixed dose of modified FOLFOX 6 (mFOLFOX6) chemotherapy regimen in the phase 2 part of the study. Phase 1 study details and results are reported separately (NCT03343301); Phase 2 study results are reported below.
Pre-assignment Detail	Participants were randomized equally to one of two treatment groups stratified based on the following factors: Geographic region: United States/European Union, China, or Rest of Asia Prior treatment status: de novo (no prior adjuvant/neo-adjuvant therapy) or prior adjuvant/neo-adjuvant therapy Administration of a single dose of mFOLFOX6 prior to enrollment: Yes or No.

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received modified FOLFOX (mFOLFOX6) chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Period Title: Overall Study
STARTED	77	78
Received Any Study Treatment	76	77
COMPLETED	0	0
NOT COMPLETED	77	78

Baseline Characteristics

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6	Total
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Total of all reporting groups
Overall Participants	77	78	155
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	58 75.3%	53 67.9%	111 71.6%
>=65 years	19 24.7%	25 32.1%	44 28.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.0 (11.11)	59.1 (12.04)	58.5 (11.56)
Sex: Female, Male (Count of Participants)
Female	25 32.5%	19 24.4%	44 28.4%
Male	52 67.5%	59 75.6%	111 71.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.6%	3 3.8%	5 3.2%
Not Hispanic or Latino	74 96.1%	75 96.2%	149 96.1%
Unknown or Not Reported	1 1.3%	0 0%	1 0.6%
Race/Ethnicity, Customized (Count of Participants)
Asian	45 58.4%	44 56.4%	89 57.4%
Black or African American	0 0%	1 1.3%	1 0.6%
American Indian or Alaska Native	0 0%	1 1.3%	1 0.6%
White	30 39%	31 39.7%	61 39.4%
Other	2 2.6%	1 1.3%	3 1.9%
Geographic Region (Count of Participants)
United States / European Union	32 41.6%	34 43.6%	66 42.6%
China	14 18.2%	13 16.7%	27 17.4%
Rest of Asia	31 40.3%	31 39.7%	62 40%
Prior Treatment Status (Count of Participants)
Prior adjuvant/neo-adjuvant therapy	14 18.2%	13 16.7%	27 17.4%
No prior adjuvant/neo-adjuvant therapy	63 81.8%	65 83.3%	128 82.6%
Administration of a Single Dose of mFOLFOX6 Prior to Enrollment (Count of Participants)
Yes	35 45.5%	36 46.2%	71 45.8%
No	42 54.5%	42 53.8%	84 54.2%
Site of Primary Cancer (Count of Participants)
Gastric cancer	66 85.7%	71 91%	137 88.4%
Gastroesophageal junction cancer	11 14.3%	7 9%	18 11.6%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0 (Fully active)	25 32.5%	28 35.9%	53 34.2%
1 (Restricted activity but ambulatory)	52 67.5%	50 64.1%	102 65.8%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had ≥ 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization. The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.
Time Frame	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Measure Participants	77	78
Median (95% Confidence Interval) [months]	9.5	7.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bemarituzumab + mFOLFOX6, Placebo + mFOLFOX6
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0727
	Comments
	Method	Stratified log-rank test
	Comments	Adjusted for randomization stratification factors of geographic region and administration of mFOLFOX6 single dose prior to randomization.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio and 95% CIs were calculated using the Cox proportional hazards model, adjusted for randomization stratification factors, including geographic region and administration of mFOLFOX6 single dose prior to randomization.

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as time from randomization until death from any cause. Participants who were lost to follow-up or did not have a date of death were censored at the last date that they were known to be alive. Participants with confirmed death or alive status after the data cutoff date were censored at the data cutoff date.
Time Frame	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Measure Participants	77	78
Median (95% Confidence Interval) [months]	NA	12.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bemarituzumab + mFOLFOX6, Placebo + mFOLFOX6
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0268
	Comments
	Method	Stratified log-rank test
	Comments	Adjusted for randomization stratification factors, including geographic region and administration of mFOLFOX6 single dose prior to randomization.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.35 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio and 95% CIs were calculated using the Cox proportional hazards model, adjusted for randomization stratification factors, including geographic region and administration of mFOLFOX6 single dose prior to randomization.

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Tumor response assessment was performed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. ORR is defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions.
Time Frame	Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.

Outcome Measure Data

Analysis Population Description

Intent-to-treat population

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Measure Participants	77	78
Number (95% Confidence Interval) [percentage of participants]	46.8 60.8%	33.3 42.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bemarituzumab + mFOLFOX6, Placebo + mFOLFOX6
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1060
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	P-value was calculated based on stratum-adjusted Cochran-Mantel-Haenszel (CMH) proportions
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	13.1
	Confidence Interval	(2-Sided) 95%; -2.8 to 29.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events
Description	Treatment emergent adverse events are defined as adverse events (AEs) that started or worsened between the start of study drug and 28 days after permanent discontinuation of study drug. A serious AE is defined as any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability or incapacity; Was a congenital anomaly or birth defect. The investigator assessed the causality/relationship between the study treatment and each AE, and assessed the severity of each AE according to the guidelines provided in National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5).
Time Frame	From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 75.0) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 75.6) weeks in the placebo + mFOLFOX6 group.

Outcome Measure Data

Analysis Population Description

Safety population includes all participants who received any portion of at least 1 dose of study treatment (bemarituzumab + mFOLFOX6 or placebo + mFOLFOX6).

Arm/Group Title	Bemarituzumab + mFOLFOX6	Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.	Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Measure Participants	76	77
Any treatment-emergent adverse event (TEAE)	76 98.7%	76 97.4%
TEAE with Grade ≥ 3	63 81.8%	57 73.1%
TEAE related to any study drug	72 93.5%	73 93.6%
TEAE with Grade ≥ 3 related to study drug	57 74%	47 60.3%
Serious adverse event (SAE)	24 31.2%	28 35.9%
SAE related to any study drug	11 14.3%	15 19.2%
TEAE leading to bemarituzumab/placebo discontinuation	26 33.8%	4 5.1%
TEAE leading to any component of mFOLFOX6 discontinuation	35 45.5%	28 35.9%
TEAE leading to bemarituzumab/placebo reduction	9 11.7%	7 9%
TEAE leading to death (Grade 5)	5 6.5%	4 5.1%

Adverse Events

Time Frame	All-cause mortality: From randomization until the end of study; median (min, max) time on study was 43 (0.6, 95.4) weeks in the Placebo + mFOLFOX6 group and 52 (0.1, 90.9) weeks in the Bemarituzumab + mFOLFOX6 group. Adverse Events: From first dose of any study drug to 28 days after last dose; actual median (min, max) duration of treatment emergent period was 28 (4.3, 75.6) weeks in the Placebo + mFOLFOX6 group and 29 (4.1, 75.0) weeks in the Bemarituzumab+ mFOLFOX6 group.
Adverse Event Reporting Description	All-cause mortality is reported for all participants randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Arm/Group Title	Bemarituzumab + mFOLFOX6		Placebo + mFOLFOX6
Arm/Group Description	Participants received 15 mg/kg bemarituzumab administered Q2W with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.		Participants received placebo for bemarituzumab administered Q2W with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
All Cause Mortality
	Bemarituzumab + mFOLFOX6		Placebo + mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/77 (36.4%)		41/78 (52.6%)
Serious Adverse Events
	Bemarituzumab + mFOLFOX6		Placebo + mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/76 (31.6%)		28/77 (36.4%)
Blood and lymphatic system disorders
Anaemia	2/76 (2.6%)		1/77 (1.3%)
Febrile neutropenia	0/76 (0%)		2/77 (2.6%)
Leukopenia	1/76 (1.3%)		0/77 (0%)
Neutropenia	0/76 (0%)		1/77 (1.3%)
Cardiac disorders
Acute myocardial infarction	0/76 (0%)		1/77 (1.3%)
Coronary artery disease	1/76 (1.3%)		0/77 (0%)
Gastrointestinal disorders
Abdominal pain	1/76 (1.3%)		1/77 (1.3%)
Ascites	0/76 (0%)		1/77 (1.3%)
Constipation	0/76 (0%)		2/77 (2.6%)
Diarrhoea	0/76 (0%)		1/77 (1.3%)
Dysphagia	0/76 (0%)		1/77 (1.3%)
Enterocolitis	0/76 (0%)		1/77 (1.3%)
Gastric perforation	0/76 (0%)		1/77 (1.3%)
Ileus	2/76 (2.6%)		2/77 (2.6%)
Mechanical ileus	1/76 (1.3%)		0/77 (0%)
Nausea	0/76 (0%)		1/77 (1.3%)
Oesophageal perforation	1/76 (1.3%)		0/77 (0%)
Stomatitis	1/76 (1.3%)		0/77 (0%)
Upper gastrointestinal haemorrhage	0/76 (0%)		1/77 (1.3%)
Vomiting	2/76 (2.6%)		2/77 (2.6%)
General disorders
Asthenia	0/76 (0%)		2/77 (2.6%)
Death	0/76 (0%)		1/77 (1.3%)
Incarcerated hernia	0/76 (0%)		1/77 (1.3%)
Pyrexia	1/76 (1.3%)		3/77 (3.9%)
Hepatobiliary disorders
Cholecystitis	0/76 (0%)		1/77 (1.3%)
Jaundice cholestatic	1/76 (1.3%)		0/77 (0%)
Immune system disorders
Anaphylactic reaction	1/76 (1.3%)		1/77 (1.3%)
Drug hypersensitivity	0/76 (0%)		1/77 (1.3%)
Hypersensitivity	2/76 (2.6%)		0/77 (0%)
Infections and infestations
Biliary tract infection	1/76 (1.3%)		0/77 (0%)
Pneumonia	2/76 (2.6%)		3/77 (3.9%)
Pneumonia bacterial	0/76 (0%)		1/77 (1.3%)
Sepsis	2/76 (2.6%)		1/77 (1.3%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/76 (0%)		1/77 (1.3%)
Infusion related reaction	1/76 (1.3%)		1/77 (1.3%)
Procedural complication	1/76 (1.3%)		0/77 (0%)
Investigations
Alanine aminotransferase increased	0/76 (0%)		1/77 (1.3%)
Aspartate aminotransferase increased	0/76 (0%)		1/77 (1.3%)
Neutrophil count decreased	1/76 (1.3%)		2/77 (2.6%)
Transaminases increased	0/76 (0%)		1/77 (1.3%)
White blood cell count decreased	0/76 (0%)		2/77 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	1/76 (1.3%)		1/77 (1.3%)
Failure to thrive	0/76 (0%)		1/77 (1.3%)
Hypokalaemia	0/76 (0%)		1/77 (1.3%)
Hypomagnesaemia	0/76 (0%)		1/77 (1.3%)
Hypophagia	0/76 (0%)		1/77 (1.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/76 (0%)		1/77 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	0/76 (0%)		1/77 (1.3%)
Tumour haemorrhage	0/76 (0%)		2/77 (2.6%)
Nervous system disorders
Headache	1/76 (1.3%)		0/77 (0%)
Product Issues
Device issue	0/76 (0%)		1/77 (1.3%)
Psychiatric disorders
Completed suicide	0/76 (0%)		1/77 (1.3%)
Renal and urinary disorders
Acute kidney injury	0/76 (0%)		1/77 (1.3%)
Hydronephrosis	0/76 (0%)		1/77 (1.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/76 (1.3%)		0/77 (0%)
Pneumonia aspiration	0/76 (0%)		1/77 (1.3%)
Pulmonary embolism	1/76 (1.3%)		0/77 (0%)
Vascular disorders
Embolism	1/76 (1.3%)		0/77 (0%)
Hypovolaemic shock	0/76 (0%)		1/77 (1.3%)
Other (Not Including Serious) Adverse Events
	Bemarituzumab + mFOLFOX6		Placebo + mFOLFOX6
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/76 (98.7%)		75/77 (97.4%)
Blood and lymphatic system disorders
Anaemia	25/76 (32.9%)		26/77 (33.8%)
Leukopenia	8/76 (10.5%)		9/77 (11.7%)
Neutropenia	15/76 (19.7%)		13/77 (16.9%)
Thrombocytopenia	11/76 (14.5%)		4/77 (5.2%)
Eye disorders
Cataract	7/76 (9.2%)		1/77 (1.3%)
Corneal disorder	4/76 (5.3%)		0/77 (0%)
Corneal epithelium defect	6/76 (7.9%)		0/77 (0%)
Dry eye	20/76 (26.3%)		5/77 (6.5%)
Keratitis	11/76 (14.5%)		1/77 (1.3%)
Limbal stem cell deficiency	6/76 (7.9%)		0/77 (0%)
Punctate keratitis	10/76 (13.2%)		2/77 (2.6%)
Vision blurred	12/76 (15.8%)		1/77 (1.3%)
Gastrointestinal disorders
Abdominal distension	4/76 (5.3%)		6/77 (7.8%)
Abdominal pain	16/76 (21.1%)		18/77 (23.4%)
Abdominal pain upper	6/76 (7.9%)		5/77 (6.5%)
Constipation	22/76 (28.9%)		24/77 (31.2%)
Diarrhoea	31/76 (40.8%)		23/77 (29.9%)
Dyspepsia	7/76 (9.2%)		9/77 (11.7%)
Nausea	36/76 (47.4%)		41/77 (53.2%)
Stomatitis	24/76 (31.6%)		10/77 (13%)
Vomiting	22/76 (28.9%)		23/77 (29.9%)
General disorders
Asthenia	19/76 (25%)		14/77 (18.2%)
Fatigue	15/76 (19.7%)		20/77 (26%)
Mucosal inflammation	9/76 (11.8%)		4/77 (5.2%)
Oedema peripheral	3/76 (3.9%)		4/77 (5.2%)
Pyrexia	8/76 (10.5%)		12/77 (15.6%)
Infections and infestations
Conjunctivitis	5/76 (6.6%)		2/77 (2.6%)
Onychomycosis	4/76 (5.3%)		0/77 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	6/76 (7.9%)		7/77 (9.1%)
Investigations
Alanine aminotransferase increased	22/76 (28.9%)		11/77 (14.3%)
Aspartate aminotransferase increased	23/76 (30.3%)		15/77 (19.5%)
Blood alkaline phosphatase increased	7/76 (9.2%)		5/77 (6.5%)
Blood bilirubin increased	5/76 (6.6%)		4/77 (5.2%)
Neutrophil count decreased	31/76 (40.8%)		33/77 (42.9%)
Platelet count decreased	14/76 (18.4%)		21/77 (27.3%)
Weight decreased	16/76 (21.1%)		10/77 (13%)
Weight increased	0/76 (0%)		4/77 (5.2%)
White blood cell count decreased	16/76 (21.1%)		12/77 (15.6%)
Metabolism and nutrition disorders
Decreased appetite	23/76 (30.3%)		28/77 (36.4%)
Hypoalbuminaemia	4/76 (5.3%)		9/77 (11.7%)
Hypokalaemia	4/76 (5.3%)		6/77 (7.8%)
Hypomagnesaemia	4/76 (5.3%)		1/77 (1.3%)
Hyponatraemia	5/76 (6.6%)		4/77 (5.2%)
Musculoskeletal and connective tissue disorders
Myalgia	4/76 (5.3%)		4/77 (5.2%)
Pain in extremity	0/76 (0%)		4/77 (5.2%)
Nervous system disorders
Dizziness	6/76 (7.9%)		4/77 (5.2%)
Dysgeusia	5/76 (6.6%)		6/77 (7.8%)
Headache	7/76 (9.2%)		3/77 (3.9%)
Neuropathy peripheral	13/76 (17.1%)		11/77 (14.3%)
Neurotoxicity	2/76 (2.6%)		5/77 (6.5%)
Paraesthesia	13/76 (17.1%)		10/77 (13%)
Peripheral sensory neuropathy	15/76 (19.7%)		15/77 (19.5%)
Psychiatric disorders
Insomnia	2/76 (2.6%)		6/77 (7.8%)
Respiratory, thoracic and mediastinal disorders
Cough	8/76 (10.5%)		8/77 (10.4%)
Epistaxis	17/76 (22.4%)		3/77 (3.9%)
Rhinorrhoea	3/76 (3.9%)		5/77 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	5/76 (6.6%)		6/77 (7.8%)
Nail disorder	6/76 (7.9%)		1/77 (1.3%)
Onycholysis	4/76 (5.3%)		0/77 (0%)
Onychomadesis	5/76 (6.6%)		1/77 (1.3%)
Palmar-plantar erythrodysaesthesia syndrome	5/76 (6.6%)		1/77 (1.3%)
Pruritus	8/76 (10.5%)		8/77 (10.4%)
Rash	4/76 (5.3%)		2/77 (2.6%)
Urticaria	4/76 (5.3%)		3/77 (3.9%)
Vascular disorders
Hypertension	1/76 (1.3%)		5/77 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The CTA generally does not restrict an investigator's discussion of trial results after completion. Amgen has limited time to review material discussing trial results (up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control/approval of content. For multicenter studies, PI agrees not to publish results before first multi-center publication for at least 18 mo after study completion at all sites & all analyses of data resulting from Study.